Interaction of metargidin (ADAM-15) with alpha(v)beta(3) and alpha(5)beta(1) integrins on different haemopoietic cells

Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to th e ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this fami ly contain an amino-terminal metalloprotease domain followed by a disintegr in domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, s uggesting that it may potentially interact with the integrin family of prot eins, Here we identify integrin ligands for metargidin on haemopoietic cell s, by using a chimeric protein containing the extracellular domain of metar gidin fused to the Fc portion of human IgG, Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargid in bound to a monocytic cell line, U937, and a T cell line, MOLT-4 in a spe cific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alpha(v)beta(3) is a liga nd for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integri n alpha(5)beta(1) contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell bind ing to both cell lines. The specificity of the interaction between both alp ha(v)beta(3) and alpha(5)beta(1) and metargidin was further confirmed by so lid-phase adhesion assays using purified recombinant integrins. These resul ts together indicate that metargidin can function as a cell adhesion molecu le via interactions with alpha(v)beta(3) and alpha(5)beta(1) integrins.